Thernanostic agents are agents that can simultaneously perform therapy and diagnostics using a single platform. Theranostic agents are typically nanoparticles or microparticles with additional functionalities that confer both diagnostic and therapeutic capabilities to the agent. A variety of particle-based theranostic agents have been described (Xie et al., 2010) including, iron oxide, gold, quantum dot, carbon nanotube and silica particle-based theranostic agents. Here we describe a coordination polymer, particle-based theranostic agents.
Coordination polymers having their general structure involving a network of metal ions linked orthogonally by cyanide bridges are commonly referred as Prussian blue analogs or belonging to the Prussian blue family. Prussian blue is a synthetic dye that was synthesized in the early 18th century. Chemically, Prussian blue is iron (III) hexacyanoferrate (II) and exists in two forms—a “soluble” form that can be stably dispersed as a colloid in water (though it is insoluble in water) with a structural formula KFe3[Fe(CN)6] and an “insoluble” form with a structural formula Fe4[Fe(CN)6], that cannot be stably dispersed as a colloid in water. The insoluble form of Prussian blue Fe4[Fe(CN)6] is sold as an FDA approved drug RADIOGARDASE® by Heyltex Corporation (RADIOGARDASE® drug label; FDA website). Radiogardase contains 0.5 grams of insoluble Prussian blue powder in gelatin capsules containing 0-38 mg of microcrystalline cellulose. It is used for treating patients who are suspected or known to have internal contamination with radioactive/non-radioactive thallium or radioactive cesium to increase the elimination rates of the said elements from the body of treated patients.
Most forms of coordination polymers belonging to the Prussian blue family have a high affinity for cations, which they mechanically trap, adsorb or sequester via cation exchange. This ion sequestration ability of especially the “soluble” form of Prussian blue has been tapped by various groups to synthesize medical contrast agents. Methods have been described to synthesize Prussian blue nanoparticles and their use as MRI contrast agents in the literature (Hornok and Dekany, 2007; Shokouhimehr et al, 2010a, 2010b, 2010c, Huang SP 2010, 2012). Kawamoto et al. in U.S. Pat. No. 7,687,188 B2 disclose a method for producing ultrafine particles of a Prussian blue-type metal complex but do not describe in specific imaging uses. Huang et al. in U.S. Pat. No. 8,092,783 B2 describe gadolinium containing Prussian blue nanoparticles for use as a non-toxic MRI contrast agent but they do not describe other imaging or therapeutic uses for the gadolinium containing Prussian blue nanoparticles. Mathe et al. in WO/2012/110835 describe Prussian blue based nanoparticles with a generalized structure AxN′n[M(CN)6] surrounded by metal isotopes and an organic biocompatible coating. Further, they describe the use of their said agent for multimodal imaging, cancer cell and tumor detection and therapy.
Described herein are novel compounds having a Prussian blue analog lattice compound represented by a generalized structural formula AxByM4[M′(CN)6]z.nH2O and the synthesis thereof. The incorporation of elements B within the Prussian blue-type lattice along with the water molecules of the core, provide surprisingly superior imaging capabilities than the constructs described above.